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February 18, 2014
08:13 EDTMACKMerrimack MM-141 preclinical study published in Molecular Cancer Therapeutics
Merrimack Pharmaceuticals announced that the manuscript "MM-141, an IGF-1R- and ErbB3-Directed Bispecific Antibody, Overcomes Network Adaptations That Limit Activity of IGF-1R Inhibitors" has been published in Molecular Cancer Therapeutics and selected for the Highlights section in the current issue . This publication describes the preclinical development of Merrimack's MM-141, a novel bispecific tetravalent antibody that binds to IGF-1R and ErbB3 receptors. With this mechanism, MM-141 is able to inhibit oncogenic signaling through the PI3K/AKT/mTOR pathway, which is a driving force behind cell growth. MM-141 recently completed the monotherapy portion of a Phase 1 study in the United States and Europe. It is currently being investigated in a Phase 1 combination study and is expected to enter Phase 2 development in 2014. IGF-1R, the receptor activated by insulin-like growth factor 1, has the ability to induce cellular growth and proliferation. Thus, it has been implicated in promoting resistance to both chemotherapies and targeted therapies. However, the effectiveness of current IGF-1R inhibitors in the clinic has been limited, as cancer cells have the ability to develop resistance to therapies by signaling through alternative pathways. Through a systems biology-based methodology, Merrimack researchers have found that cancer cells can develop resistance to IGF-1R that is mediated through ErbB3. Therefore, dual inhibition of IGF-1R and ErbB3 pathways would be necessary to block the PI3K/AKT/mTOR pathway, resulting in the arrest of tumor cell growth. In preclinical in vitro and in vivo models, MM-141 was more active than a combination of anti-ErbB3 and anti-IGF-1R monoclonal antibodies. MM-141 was able to inhibit PI3K/AKT/mTOR signaling and potentiated the activity of cytotoxic and targeted therapies, supporting its ongoing clinical development.
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December 17, 2014
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December 12, 2014
08:05 EDTMACKMerrimack presents research on MM-398, MM-302, MM-121
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